Global epidemiology and clinical outcomes of carbapenem-resistant Pseudomonas aeruginosa and associated carbapenemases (POP): a prospective cohort study
Authors: Jinnethe Reyes, Lauren Komarow, Liang Chen, Lizhao Ge, Blake M Hanson, Eric Cober, Erica Herc, Thamer Alenazi, Keith S Kaye, Julia Garcia-Diaz, Lanjuan Li, Souha S Kanj, Zhengyin Liu, Jose M Oñate, Robert A Salata, Kalisvar Marimuthu, Hainv Gao, Zhiyong Zong, Sandra L Valderrama-Beltrán, Yunsong Yu, Paul Tambyah, Gregory Weston, Soraya Salcedo, Lillian M Abbo, Qing Xie, Karen Ordoñez, Minggui Wang, Martin E Stryjewski, Jose M Munita, David L Paterson, Scott Evans, Carol Hill, Keri Baum, Robert A Bonomo, Barry N Kreiswirth, Maria Virginia Villegas, Robin Patel, Cesar A Arias, Henry F Chambers, Vance G Fowler, Yohei Doi, David van Duin, Michael J Satlin, Jinnethe Reyes, Lauren Komarow, Liang Chen, Lizhao Ge, Blake Hanson, Eric Cober, Erica Herc, Thamer Alenazi, Keith Kaye, Julia Garcia-Diaz, Lanjuan Li, Souha Kanj, Zhengyin Liu, Jose Oñate, Robert Salata, Kalisvar Marimuthu, Hainv Gao, Zhiyong Zong, Sandra Valderrama-Beltrán, Yunsong Yu, Paul Tambyah, Gregory Weston, Soraya Salcedo, Lillian Abbo, Qing Xie, Karen Ordoñez, Minggui Wang, Martin Stryjewski, Jose Munita, David Paterson, Scott Evans, Carol Hill, Keri Baum, Robert Bonomo, Barry Kreiswirth, Maria Virginia Villegas, Robin Patel, Cesar Arias, Henry Chambers, Vance Fowler, Yohei Doi, David van Duin, Michael Satlin
Journal: The Lancet Microbe (2023)

BackgroundCarbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical significance of carbapenemases are unclear. The aim of this study was to define characteristics and outcomes of CRPA infections and the global frequency and clinical impact of carbapenemases harboured by CRPA.MethodsWe conducted an observational, prospective cohort study of CRPA isolated from bloodstream, respiratory, urine, or wound cultures of patients at 44 hospitals (10 countries) between Dec 1, 2018, and Nov 30, 2019. Clinical data were abstracted from health records and CRPA isolates were whole-genome sequenced. The primary outcome was 30-day mortality from the day the index culture was collected. We compared outcomes of patients with CRPA infections by infection type and across geographic regions and performed an inverse probability weighted analysis to assess the association between carbapenemase production and 30-day mortality.FindingsWe enrolled 972 patients (USA n=527, China n=171, south and central America n=127, Middle East n=91, Australia and Singapore n=56), of whom 581 (60%) had CRPA infections. 30-day mortality differed by infection type (bloodstream 21 [30%] of 69, respiratory 69 [19%] of 358, wound nine [14%] of 66, urine six [7%] of 88; p=0·0012) and geographical region (Middle East 15 [29%] of 52, south and central America 20 [27%] of 73, USA 60 [19%] of 308, Australia and Singapore three [11%] of 28, China seven [6%] of 120; p=0·0002). Prevalence of carbapenemase genes among CRPA isolates also varied by region (south and central America 88 [69%] of 127, Australia and Singapore 32 [57%] of 56, China 54 [32%] of 171, Middle East 27 [30%] of 91, USA ten [2%] of 527; p<0·0001). KPC-2 (n=103 [49%]) and VIM-2 (n=75 [36%]) were the most common carbapenemases in 211 carbapenemase-producing isolates. After excluding USA patients, because few US isolates had carbapenemases, patients with carbapenemase-producing CRPA infections had higher 30-day mortality than those with non-carbapenemase-producing CRPA infections in both unadjusted (26 [22%] of 120 vs 19 [12%] of 153; difference 9%, 95% CI 3–16) and adjusted (difference 7%, 95% CI 1–14) analyses.InterpretationThe emergence of different carbapenemases among CRPA isolates in different geographical regions and the increased mortality associated with carbapenemase-producing CRPA infections highlight the therapeutic challenges posed by these organisms.FundingNational Institutes of Health.